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The distinct structural alterations in white matter (WM) in patients with \u03b1\u2010synucleinopathies experiencing OH, alongside their association with other non\u2010motor symptoms, remain unexplored. This study employs axial diffusivity and density imaging (NODDI) to investigate WM damage specific to \u03b1\u2010synucleinopathies with concurrent OH, delivering fresh evidence to supplement our understanding of the pathogenic mechanisms and pathological rationales behind the occurrence of a spectrum of non\u2010motor functional impairments in \u03b1\u2010synucleinopathies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study recruited 49 individuals diagnosed with \u03b1\u2010synucleinopathies, stratified into an \u03b1\u2010OH group (<jats:italic>n<\/jats:italic>\u2009=\u200924) and an \u03b1\u2010NOH group (without OH, <jats:italic>n<\/jats:italic>\u2009=\u200925). Additionally, 17 healthy controls were included for supine and standing blood pressure data collection, as well as neuropsychological assessments. Magnetic resonance imaging (MRI) was utilized for the calculation of NODDI parameters, and tract\u2010based spatial statistics (TBSS) were employed to explore differential clusters. The fibers covered by these clusters were defined as regions of interest (ROI) for the extraction of NODDI parameter values and the analysis of their correlation with neuropsychological scores.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The TBSS analysis unveiled specific cerebral regions exhibiting disparities within the \u03b1\u2010OH group as compared to both the \u03b1\u2010NOH group and the healthy controls. These differences were evident in clusters that indicated a decrease in the acquisition of the neurite density index (NDI), a reduction in the orientation dispersion index (ODI), and an increase in the isotropic volume fraction (FISO) (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). The extracted values from these ROIs demonstrated significant correlations with clinically assessed differences in supine and standing blood pressure, overall cognitive scores, and anxiety\u2010depression ratings (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Patients with \u03b1\u2010synucleinopathies experiencing OH exhibit distinctive patterns of microstructural damage in the WM as revealed by the NODDI model, and there is a correlation with the onset and progression of non\u2010motor functional impairments.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14712","type":"journal-article","created":{"date-parts":[[2024,4,14]],"date-time":"2024-04-14T20:55:20Z","timestamp":1713128120000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Brain white matter changes and their associations with <scp>non\u2010motor<\/scp> dysfunction in orthostatic hypotension in <scp>\u03b1\u2010synucleinopathy<\/scp>: A <scp>NODDI<\/scp> study"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3018-494X","authenticated-orcid":false,"given":"Lin","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Neurology, Center for Cognitive Neurology Fujian Medical University Union Hospital  Fuzhou City China"},{"name":"Fujian Institute of Geriatrics Fujian Medical University Union Hospital  Fuzhou City China"},{"name":"Institute of Clinical Neurology Fujian Medical University  Fuzhou City China"},{"name":"Fujian Key Laboratory of Molecular Neurology Fujian Medical University  Fuzhou City China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peilin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Center for Cognitive Neurology Fujian Medical University Union Hospital  Fuzhou City China"},{"name":"Fujian Institute of Geriatrics Fujian 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